title: Discovery of a potent peptidic cyclophilin A inhibitor Trp-Gly-Pro.
abstract: Through virtual screening of a rationally built database consisting of 40 peptides, we identified three short peptides. After testing these three synthetic peptides, we found that the peptide Trp-Gly-Pro (WGP) showed comparable inhibitory ability as positive control cyclosporine A (CsA) on CypA-mediated PPIase activity with IC50 values of 33.11 nM and 10.25 nM, respectively. The peptide WGP had same order of CypA-binding affinity as CsA with dissociation equilibrium constant KD of 3.41×10(-6) and 6.42×10(-6) M, respectively. This peptide could also inhibit HIV-1IIIB infection. This study provides a novel strategy for rational design and development of peptidic drugs.
authors.affiliation: State Key Laboratory of Surface Physics, Department of Physics, Fudan University, Shanghai 200433, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Pang
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhang
authors.forename: Linxiang
authors.initials: L
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Wu
authors.initials: W
authors.lastname: He
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002461:Cell Line, Transformed; D021984:Cyclophilin A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D009842:Oligopeptides; D021984:Cyclophilin A